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C/EBP beta, when expressed from the C/ebp alpha gene locus, can functionally replace C/EBP alpha in liver but not in adipose tissue

  1. Author:
    Chen, S. S.
    Chen, J. F.
    Johnson, P. F.
    Muppala, V.
    Lee, Y. H.

  2. Author Address

    Acad Sinica, Inst Mol Biol, Lab Mol Pathol, Taipei 115, Taiwan. Acad Sinica, Inst Mol Biol, Lab Mol Pathol, Taipei 115, Taiwan. NCI, Eukaryot Transcript Regulat Sect, Regulat Cell Growth Lab, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA.
    1. Year: 2000
  2. Journal: Molecular and Cellular Biology
    1. 20
    2. 19
    3. Pages: 7292-7299
  4. Type of Article: Article
  1. Abstract:

    Knockout of C/EBP alpha causes a severe loss of liver function and, subsequently, neonatal lethality in mire. By using a gene replacement approach, we generated a new C/EBP alpha-null mouse strain in which C/EBP beta, in addition to its own expression, substituted for C/EBP alpha expression in tissues. The homozygous mutant mice C/ebp alpha(beta/beta) are viable and fertile and show none of the overt liver abnormalities found in the previous C/EBP alpha-null mouse line. Levels of hepatic PEPCK mRNA are not different between C/ebp alpha(beta/beta) and wild-type mice. However, despite their normal growth rate, C/ebp alpha(beta/beta) mice have markedly reduced fat storage in their white adipose tissue (WAT). Expression of two adipocyte-specific factors, adipsin and leptin, is significantly reduced in the WAT of C/ebp alpha(beta/beta) mice. In addition, expression of the non-adipocyte-specific genes for transferrin and cysteine dioxygenase is reduced in WAT but not in liver. Our study demonstrates that when expressed from the C/ebp alpha gene locus, C/EBP beta can act for C/EBP alpha to maintain liver functions during development. Moreover, our studies with the C/ebp alpha(beta/beta) mice provide new insights into the nonredundant functions of C/EBP alpha and C/EBP beta on gene regulation in WAT.

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